Early postburn lipid peroxidation: effect of ibuprofen and allopurinol.
We measured lipid peroxidation of plasma, lung, and liver in anaesthetized sheep after third-degree burns involving 30% of total body surface. Animals were resuscitated to baseline filling pressures with lactated Ringer's solution and killed 10 hours after burn. Six sheep were pretreated with ibuprofen (12.5 mg/kg) and five with allopurinol (50 mg/kg). We used conjugated dienes and malondialdehyde as measures of lipid peroxidation. Circulating conjugated dienes increased from a baseline of 0.48 +/- 0.06 to 0.64 +/- 0.05 after burn, while protein-rich burn tissue lymph flow increased up to eightfold. We also noted a significant increase in lung tissue malondialdehyde from 45 +/- 4 to 60 +/- 6 nmol/gm and liver malondialdehyde from 110 +/- 20 to 271 +/- 34 nmol/gm along with increased tissue neutrophil sequestration. Ibuprofen attenuated lung-tissue malondialdehyde but had no effect on lung inflammation, circulating lipid peroxides or burn edema, indicating that ibuprofen most likely decreased O2 radical release in lung tissue by the already-sequestered neutrophils. Allopurinol, possibly via xanthine oxidase inhibition, markedly attenuated burn QL and circulating lipid peroxides and prevented all pulmonary lipid peroxidation and inflammation, indicating that release of oxidant from burn tissue was in part responsible for local burn edema, as well as distant inflammation and oxidant release, the latter most likely from complement activation. Neither antioxidant decreased lipid peroxidation in the liver; this indicates that its mechanism of production was different from that seen in burn tissue, in plasma, or in the lung. An ischemic event resulting from a selective decrease in splanchnic blood flow may be the cause of the liver changes.
Demling
R H
RH
Harvard Medical School, Longwood Area Trauma Center, Boston, MA 02115.
LaLonde
C
C
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D002056:Burns / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004487:Edema / Q000517:prevention & control; D007052:Ibuprofen / Q000627:therapeutic use*; D007249:Inflammation; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D012016:Reference Values; D012756:Sheep
D008315:Malondialdehyde; D000493:Allopurinol; D007052:Ibuprofen